1k2i: Difference between revisions
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< | ==Crystal Structure of Gamma-Chymotrypsin in Complex with 7-Hydroxycoumarin== | ||
<StructureSection load='1k2i' size='340' side='right'caption='[[1k2i]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1k2i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K2I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K2I FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SN1:2,4-DIHYDROXY-TRANS+CINNAMIC+ACID'>SN1</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1k2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k2i OCA], [https://pdbe.org/1k2i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k2i RCSB], [https://www.ebi.ac.uk/pdbsum/1k2i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k2i ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CTRA_BOVIN CTRA_BOVIN] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k2/1k2i_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1k2i ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The 1.8 A crystal structure of 7-hydroxycoumarin (7-HC) bound to chymotrypsin reveals that this inhibitor forms a planar cinnamate acyl-enzyme complex. The phenyl ring of the bound inhibitor forms numerous van der Waals contacts in the S1 pocket of the enzyme, with the p-hydroxyl group donating a hydrogen bond to the main-chain oxygen atom of Ser217, and the o-hydroxyl group forming a water-mediated hydrogen bond with the carbonyl oxygen of Val227. The structure of the acyl-enzyme complex suggests that the mechanism of inhibition of 7-HC involves nucleophilic attack by the Ser195 O(gamma) atom on the carbonyl carbon atom of the inhibitor, accompanied by the breaking of the 2-pyrone ring of the inhibitor, and leading to the formation of a cinnamate acyl-enzyme derivative via a tetrahedral transition state. Comparisons with structures of photoreversible cinnamates bound to chymotrypsin reveal that although 7-HC interacts with the enzyme in a similar fashion, the binding of 7-HC to chymotrypsin takes place in a productive conformation in contrast to the photoreversible cinnamates. In summary, the 7-HC-chymotrypsin complex provides basic insight into the inhibition of chymotrypsin by natural coumarins and provides a structural basis for the design of more potent mechanism-based inhibitors against a wide range of biologically important chymotrypsin-like enzymes. | |||
Crystal structure of gamma-chymotrypsin in complex with 7-hydroxycoumarin.,Ghani U, Ng KK, Atta-ur-Rahman, Choudhary MI, Ullah N, James MN J Mol Biol. 2001 Nov 30;314(3):519-25. PMID:11846564<ref>PMID:11846564</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1k2i" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Chymotrypsin 3D structures|Chymotrypsin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
< | |||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Atta-ur-Rahman]] | [[Category: Atta-ur-Rahman]] | ||
[[Category: Choudhary | [[Category: Choudhary MI]] | ||
[[Category: Ghani | [[Category: Ghani U]] | ||
[[Category: James | [[Category: James MNG]] | ||
[[Category: Ng | [[Category: Ng KKS]] | ||
[[Category: Ullah | [[Category: Ullah N]] | ||
Latest revision as of 12:37, 25 December 2024
Crystal Structure of Gamma-Chymotrypsin in Complex with 7-HydroxycoumarinCrystal Structure of Gamma-Chymotrypsin in Complex with 7-Hydroxycoumarin
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 1.8 A crystal structure of 7-hydroxycoumarin (7-HC) bound to chymotrypsin reveals that this inhibitor forms a planar cinnamate acyl-enzyme complex. The phenyl ring of the bound inhibitor forms numerous van der Waals contacts in the S1 pocket of the enzyme, with the p-hydroxyl group donating a hydrogen bond to the main-chain oxygen atom of Ser217, and the o-hydroxyl group forming a water-mediated hydrogen bond with the carbonyl oxygen of Val227. The structure of the acyl-enzyme complex suggests that the mechanism of inhibition of 7-HC involves nucleophilic attack by the Ser195 O(gamma) atom on the carbonyl carbon atom of the inhibitor, accompanied by the breaking of the 2-pyrone ring of the inhibitor, and leading to the formation of a cinnamate acyl-enzyme derivative via a tetrahedral transition state. Comparisons with structures of photoreversible cinnamates bound to chymotrypsin reveal that although 7-HC interacts with the enzyme in a similar fashion, the binding of 7-HC to chymotrypsin takes place in a productive conformation in contrast to the photoreversible cinnamates. In summary, the 7-HC-chymotrypsin complex provides basic insight into the inhibition of chymotrypsin by natural coumarins and provides a structural basis for the design of more potent mechanism-based inhibitors against a wide range of biologically important chymotrypsin-like enzymes. Crystal structure of gamma-chymotrypsin in complex with 7-hydroxycoumarin.,Ghani U, Ng KK, Atta-ur-Rahman, Choudhary MI, Ullah N, James MN J Mol Biol. 2001 Nov 30;314(3):519-25. PMID:11846564[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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